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617 Biological relevance of C-X-C chemokines in nasal polyposis
Abstracts
J ALLERGY CLIN IMMUNOL VOLUME 105. NUMBER 1, PART 2
required to have 27 but 128 days of symptoms prior to Visit 1. Data regarding complete resolution of symptoms was obtained from the clinician-rated overall evaluation which used the following scale to rate improvement compared to Visit 1: significant improvement (complete resolution of all symptoms), moderate improvement (most symptoms resolved or improved), mild improvement (some improvement but most symptoms still present), no change (no improvement in most symptoms), mildly worse (some symptoms worse or unchanged), moderately worse (most symptoms worse), and significantly worse (all symptoms worse). A Cochran-MantelHaenszel chi-square statistic controlling for investigator was used to test the overall pattern of distribution of response within the seven response categories. There were no significant differences between treatment groups in the overall pattern of distribution for the seven response categories at endpoint (Week 7 for patients who completed the study or the last treatment visit for patients who discontinued prematurely) for Study 1. However, statistical significance was achieved in Study 2 at endpoint (p=O.O25) and approached significance (p=O.O54) at Visit 4. The results for both studies at endpoint are as follows: CLINICAN STUDY
I
SIGNIFICANT IMPROVEMENT (COMPLETE RESOLUTION) MODERATE IMPROVEMENT MILD IMPROVEMENT NO CHANGE MILDY WORSE MODERATELY WORSE SIGNIFICANTLY WORSE
OVERALL
EVALUATION
FP+CEF
PBO+CEF
N=184
N=183
STUDY 2’ FP+CEF N=166
N=162
22 (12%)
16 (9%)
49 (30%)
32 (20%)
113 (61%)
111 (61%)
72 (43%)
73 (45%)
30 (16%)
33 (18%)
18(11%)
24 (15%)
6 (3%) 8 (4%)
6 (3%) 7 (4%)
12 (7%) 12 (7%)
10 (6%) 13 (8%)
4 (2%)
7 (4%)
3 (2%)
7 (4%)
1 (Cl%)
3 (2%)
0
3 (2%)
*P&025 FOR FP+CEF VS PBG+CEF FOR THE OVERALL DISTRIBUTlON FOR THE 7 RESPONSE CATEGORIES
PBO+CEF
PATTERN OF
5207
A majority of patients in both studies had at least mild improvement in symptoms; however, few patients had complete resolution of all symptoms. Complete resolution of symptoms was experienced by a greater percentage of patients in the Fp+CEF groups in both studies. In conclusion, these studies showed that sinusitis symptoms persist after appropriate treatment has been administered for an acute episode of sinusitis, with few patients achieving complete resolution. Research Funded By A Grant From Glaxo Wellcome
617 Biological Relevance of C-X-C Chemokines in NarwJ Polyposis C Rudack*, J-M Schroederf, S Maune$, W Sroll* *Dept of ENT, Wwu Muenster, Germany tDept of Dermatology, CAU Kiel, Germany $Dept of ENT, CAU Kiel. Germany Nasal polyps, a disease entity of unknown etiology, are histologically characterized by the presence of different leukocyte types and subpopulations, especially eosinophils and neutrophils. The appearance of eosinophils and neutrophils in nasal polyps led to the working hypothesis that apart from panleukotactic factors, which attract all different leukocyte forms in a similar manner, cell-specific attractants are generated having more cell-selective chemoattractive properties. To gain insight into mechanisms that are responsible for tissue neutrophil immigration, nasal polyp tissue was analyzed for presence of of chemotactic factors showing biochemical properties known for chemokines. To sucessfully characterize biologically active chemokines in nasal polyps we extracted chemokines of nasal polyps in acidic ethanolic buffers. For further purification and detection of neutrophil chemokines biological activity we used high-performance liquid chromatography (HPLC) techniques and a bioassay measuring neutrophil chemotaxis in a Boyden chamber. The samples of nasal polyp tissue and samples of turbinate mucosa (controls) were applied to different HPLC columns (heparin-binding-, preparative RF’-8-reversed phase-, and cation-exchange column). purified chemokines were identified by gel electrophoresis and ELISA technique using a panel of monoclonal antibodies. Our results revealed that the major neutrophil attractant efficacy in nasal polyps is referred to a NAP-2 isoform, which represents a N-terminally truncated cleavage product that originate from platelet-derived precusor molecules through promolytic processing. It still has to be determined, if the biological activity of the NAP-2 isofotm is related to the C-terminally truncated isoform, which is known to be more potent than authentic NAP-2. In all, for the first time we could show that a neutrophil attractant, a NAP-2 isoform, has biological acitvity in the disease entity of Nasal Polyposis, whereas IL-8 seems to play a minor role.
J ALLERGY CLIN IMMUNOL VOLUME 105. NUMBER 1, PART 2
required to have 27 but 128 days of symptoms prior to Visit 1. Data regarding complete resolution of symptoms was obtained from the clinician-rated overall evaluation which used the following scale to rate improvement compared to Visit 1: significant improvement (complete resolution of all symptoms), moderate improvement (most symptoms resolved or improved), mild improvement (some improvement but most symptoms still present), no change (no improvement in most symptoms), mildly worse (some symptoms worse or unchanged), moderately worse (most symptoms worse), and significantly worse (all symptoms worse). A Cochran-MantelHaenszel chi-square statistic controlling for investigator was used to test the overall pattern of distribution of response within the seven response categories. There were no significant differences between treatment groups in the overall pattern of distribution for the seven response categories at endpoint (Week 7 for patients who completed the study or the last treatment visit for patients who discontinued prematurely) for Study 1. However, statistical significance was achieved in Study 2 at endpoint (p=O.O25) and approached significance (p=O.O54) at Visit 4. The results for both studies at endpoint are as follows: CLINICAN STUDY
I
SIGNIFICANT IMPROVEMENT (COMPLETE RESOLUTION) MODERATE IMPROVEMENT MILD IMPROVEMENT NO CHANGE MILDY WORSE MODERATELY WORSE SIGNIFICANTLY WORSE
OVERALL
EVALUATION
FP+CEF
PBO+CEF
N=184
N=183
STUDY 2’ FP+CEF N=166
N=162
22 (12%)
16 (9%)
49 (30%)
32 (20%)
113 (61%)
111 (61%)
72 (43%)
73 (45%)
30 (16%)
33 (18%)
18(11%)
24 (15%)
6 (3%) 8 (4%)
6 (3%) 7 (4%)
12 (7%) 12 (7%)
10 (6%) 13 (8%)
4 (2%)
7 (4%)
3 (2%)
7 (4%)
1 (Cl%)
3 (2%)
0
3 (2%)
*P&025 FOR FP+CEF VS PBG+CEF FOR THE OVERALL DISTRIBUTlON FOR THE 7 RESPONSE CATEGORIES
PBO+CEF
PATTERN OF
5207
A majority of patients in both studies had at least mild improvement in symptoms; however, few patients had complete resolution of all symptoms. Complete resolution of symptoms was experienced by a greater percentage of patients in the Fp+CEF groups in both studies. In conclusion, these studies showed that sinusitis symptoms persist after appropriate treatment has been administered for an acute episode of sinusitis, with few patients achieving complete resolution. Research Funded By A Grant From Glaxo Wellcome
617 Biological Relevance of C-X-C Chemokines in NarwJ Polyposis C Rudack*, J-M Schroederf, S Maune$, W Sroll* *Dept of ENT, Wwu Muenster, Germany tDept of Dermatology, CAU Kiel, Germany $Dept of ENT, CAU Kiel. Germany Nasal polyps, a disease entity of unknown etiology, are histologically characterized by the presence of different leukocyte types and subpopulations, especially eosinophils and neutrophils. The appearance of eosinophils and neutrophils in nasal polyps led to the working hypothesis that apart from panleukotactic factors, which attract all different leukocyte forms in a similar manner, cell-specific attractants are generated having more cell-selective chemoattractive properties. To gain insight into mechanisms that are responsible for tissue neutrophil immigration, nasal polyp tissue was analyzed for presence of of chemotactic factors showing biochemical properties known for chemokines. To sucessfully characterize biologically active chemokines in nasal polyps we extracted chemokines of nasal polyps in acidic ethanolic buffers. For further purification and detection of neutrophil chemokines biological activity we used high-performance liquid chromatography (HPLC) techniques and a bioassay measuring neutrophil chemotaxis in a Boyden chamber. The samples of nasal polyp tissue and samples of turbinate mucosa (controls) were applied to different HPLC columns (heparin-binding-, preparative RF’-8-reversed phase-, and cation-exchange column). purified chemokines were identified by gel electrophoresis and ELISA technique using a panel of monoclonal antibodies. Our results revealed that the major neutrophil attractant efficacy in nasal polyps is referred to a NAP-2 isoform, which represents a N-terminally truncated cleavage product that originate from platelet-derived precusor molecules through promolytic processing. It still has to be determined, if the biological activity of the NAP-2 isofotm is related to the C-terminally truncated isoform, which is known to be more potent than authentic NAP-2. In all, for the first time we could show that a neutrophil attractant, a NAP-2 isoform, has biological acitvity in the disease entity of Nasal Polyposis, whereas IL-8 seems to play a minor role.